ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.277G>C (p.Gly93Arg) (rs1553259691)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000638166 SCV000759652 likely pathogenic Charcot-Marie-Tooth disease, type I 2019-02-06 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 93 of the MPZ protein (p.Gly93Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with clinical features of Charcot-Marie-Tooth disease (CMT) in an affected family (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Two different missense substitutions at this codon (p.Gly93Ala, p.Gly93Glu) have been reported in individuals affected with Charcot-Marie-Tooth disease (PMID: 21326314, 9217235). These observations suggest that this novel missense substitution at this residue may affect protein function, but this has not been confirmed by published studies and the clinical significance is uncertain. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.